Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading

Objective

The quantitative parameters in the contrast-enhanced ultrasonography time–intensity curve of hepatocellular carcinoma (HCC) were studied to explore their possible implication for histological grading of HCC.

Methods

A total of 130 HCC patients (115 males and 15 females; age: 48.13±11.00 years) were studied using contrast-enhanced ultrasonography time–intensity curve and histological pathology. The quantification software Sonoliver® (TomTec Imaging Systems, Unterschleissheim, Germany) was applied to derive time–intensity curves of regions of interest in the interior of HCCs and in reference. Quantitative parameters of 115 patients were successfully obtained, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), rise slope (RS) and washout time (WT). Histological grading of HCC was performed using haematoxylin–eosin staining, and monoclonal antibodies specific for smooth muscle actin were used to observe unpaired arteries (UAs).

Results

There were significant differences among WTs in the three differentiated HCC groups (p<0.05). However, there were no significant differences among RT, TTP, RS and IMAX in the differentiated HCC groups. Moreover, the number of UAs in the differentiated HCC groups showed no statistical significance.

Conclusion

WT plays an important role in predicting well, moderately and poorly differentiated HCC.The majority of hepatocellular carcinomas (HCCs) develop through multistep hepatocarcinogenesis [1]. Various types of hepatocellular nodules are seen in cirrhotic livers. The International Working Party of the World Congress of Gastroenterology classifies hepatocellular nodules into six types: regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, well-differentiated HCC, moderately differentiated HCC and poorly differentiated HCC. The histopathological grades and types constitute well-established prognostic factors [2]. Thus, early diagnosis and confirmation of the type of hepatocellular nodules present and cellular differentiation before treatment are important.Although definite differentiation among HCC by imaging is usually impossible, the relationship between tumour cellular differentiation and image findings has been studied using contrast-enhanced (CE) CT, CEMRI and CE ultrasonography (CEUS). Tumour pathological differentiation correlates well with image findings [,3−8].Dynamic CEUS during the past decade has noticeably improved the detection and characterisation of focal liver lesions [9]. A previous study showed that CEUS and spiral CT provided a similar diagnostic accuracy in the characterisation of focal liver lesion [10]. The appearance of HCC on CEUS has also been described well. Current low-mechanical-index techniques for CEUS using second-generation microbubble agents have advantages in characterising HCC, including real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules. Some studies postulated that variations of enhancement patterns may be related to the pathological function of HCC [,5−8]. Moderately differentiated HCCs generally show classic enhancement features, with presence of hypervascularity in the arterial phase and washout during the portal phase, whereas well and poorly differentiated tumours account for most atypical variations in the arterial phase and portal venous phase [7].Reports assessing hepatocellular nodules have been based on visual analysis, despite the disadvantages of interobserver variability and low reproducibility of results. Although quantitative analysis CEUS perfusion provides more objective, reliable and reproducible results [11], the time–intensity curve (TIC) of CEUS has been obtained by quantification software for offline analysis [,12−14], from which a series of semi-quantitative perfusion parameters is extracted and analysed. An analysis of the parameters of TIC in HCC has proven the correlation of CEUS with unpaired arteries (UAs) in HCC [14]. In the present study, we compare the quantitative parameters in CEUS and UAs in different pathological gradings of HCCs to explore their possible implication for histological grading of HCC.     

Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma

Objective:

To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC).

Methods:

34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.

Results:

The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively.

Conclusion:

The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS.

Advances in knowledge:

Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.Dynamic contrast-enhanced ultrasonography (CEUS) has noticeably improved the detection and characterisation of focal liver lesions during the past decade [1]. The enhancement patterns of the lesion are evaluated in three vascular phases (the hepatic arterial, portal venous and late phases), where the hepatic arterial phase provides information on the degree and pattern of vascularity and the portal venous and late phases provide important information on the differention between benign and malignant liver lesions [1]. A previous study has shown that CEUS using SonoVue® (Bracco, Milan, Italy) and spiral-CT provides similar diagnostic accuracy in the characterisation of focal liver lesions [2].The typical enhancement of focal nodular hyperplasia (FNH) on CEUS showed hyperenhancement in the three vascular phases with a stellate vascular and centrifugal enhancement in the arterial phase or a hypoenhancing central scar in the late phase [1, 3–5]. However, these features have not been observed in all cases of FNH, particularly in small lesions. A study on FNH showed that 3 out of 13 lesions (23.1%) were hypoenhancing in the late phase [6] and 3 out of 10 lesions <3 cm had spoke-wheel patterns and 2 had central scars [4]. There is also a broad variation of stellate vascular enhancement in FNHs with a range from 27.3% to 73.3% and of central scar with a range from 36.4% to 63.3% [3–5]. Thus, it can be difficult to differentiate atypical FNHs from other hypervascular malignant tumours, such as hepatocellular carcinoma (HCC), and hypervascular metastases [3]. Furthermore, a hypoenhancing central scar has been described in fibrolamellar HCC and sclerosing or scirrhous HCC [7, 8], and a central feeding artery with spoke-wheel sign has also been described in two scirrhous HCCs [8]. Hence, a comprehensive approache rather than simply estimating the haemodynamics could be beneficial for differential diagnosis.The current low-mechanical-index techniques for CEUS are capable of real-time demonstration of continuous haemodynamic changes in both the liver and hepatocellular nodules, from which time–intensity curves can be obtained by means of analytic software and then a series of semi-quantitative perfusion measurements extracted and analysed [9–11]. This method has shown a possible benefit in diagnosing FNH by enabling analysis of the quantitative parametric curves of the five types of hypervascular liver lesions [9]. In the present study, CEUS was applied to evaluate enhancing patterns of FNH and HCC; quantitative features of CEUS in the two groups were generated with the analytic software Sonoliver® (TomTec Imaging Systems, Germany) and compared to explore their potential in the differential diagnosis. Furthermore, the quantitative analysis of CEUS was used to characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS.     

Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases

Objectives

The purpose of this prospective study was to elucidate the efficacy of using contrast-enhanced ultrasound to characterise focal hepatic lesions appearing non-hypervascular on contrast-enhanced CT in chronic liver diseases.

Methods

The study population included 22 patients with cirrhosis or chronic hepatitis, who between them had 27 focal hepatic lesions smaller than 20 mm (mean 13.9±3.4) that appeared non-hypervascular on contrast-enhanced CT. Contrast-enhanced ultrasound with perflubutane microbubble agent (Sonazoid, 0.0075 ml kg^–1) was performed prior to ultrasound-guided needle biopsy, and intensity analysis was done for hepatic lesions in the early phase (−60 s) and late phase (600 s post injection).

Results

All seven early-phase hyperenhanced lesions were hepatocellular carcinoma (HCC). 20 lesions iso- or hypoenhanced during the early phase consisted of 11 regenerative nodules (RNs) and 9 HCCs. HCC was more frequent in early-phase hyperenhanced lesions than in iso- or hypoenhanced lesions (p=0.0108). Both late-phase hypoenhanced lesions were HCCs, whereas 25 late-phase isoenhanced lesions consisted of 11 RNs and 14 HCCs. The enhancement patterns of the 11 RNs included isoenhanced appearance in both the early and late phases in 8 lesions, and early-phase hypoenhancement combined with late-phase isoenhancement in the remaining 3. Both of these enhancement patterns (i.e. either iso–iso or hypo–iso) were found in 9 malignant lesions, 9 (75%) of the 12 well-differentiated HCCs.

Conclusion

Hypervascularity on contrast-enhanced ultrasound with Sonazoid strongly suggested HCC regardless of non-hypervascularity on CT, and late-phase hypoenhancement was another possible finding of HCC. However, characterisation of hepatic lesions with other enhancement patterns was difficult using our technique.The development of hepatocellular carcinoma (HCC) has a profound influence on the prognosis of patients with chronic liver disease (CLD), and there is nearly universal consensus on the importance of adequate HCC surveillance for these patients [1,2]. However, because reliable surveillance of HCC cannot be achieved solely by assessing tumour markers such as α-fetoprotein, it is necessary to utilise currently available imaging modalities effectively and efficiently in patients at risk for developing this neoplasm [3,4]. Differential diagnosis of focal hepatic lesions is a major challenge that must be overcome in order to provide appropriate clinical management of these patients.Based on diagnostic imaging, a hypervascular appearance of focal hepatic lesions in patients with CLD strongly suggests HCC, and a hypervascular lesion larger than 20 mm can be diagnosed as HCC without performing a biopsy [1,5]. On the other hand, non-hypervascular hepatic lesions include non-malignant lesions such as regenerative nodules (RNs) and both low- and high-grade dysplastic nodules; some well-differentiated HCCs also appear as non-hypervascular lesions prior to tumour vascularisation during the multistep process of carcinogenesis [5-9]. Characterisation of non-hypervascular hepatic lesions may prove challenging in patients with CLD. For example, the invasive nature of a needle biopsy is a drawback in cirrhotic patients with impaired coagulation, so diagnostic imaging tools merit serious consideration in this clinical situation.Technical improvements in ultrasound have been outstanding in the past two decades, with the resulting advantages of real-time observation, simple technique and non-invasiveness [10]. Moreover, the use of a microbubble contrast agent allows detailed observation of tumour haemodynamics, which can prove helpful in the detection and characterisation of focal hepatic lesions [11,12]. Stable and sufficient contrast enhancement, including improved signal-to-noise ratio, is achieved in the liver using harmonic imaging in combination with a second-generation contrast agent [13].Sonazoid (GE Healthcare, Little Chalfont, UK) is a novel perflubutane microbubble contrast agent whose clinical efficacy has been demonstrated for the diagnosis of focal hepatic lesions and diffuse liver diseases [14-16]. The microbubbles of this agent are captured in the liver parenchyma during the agent''s circulation in the blood; therefore, contrast-enhanced sonography can generate both haemodynamic-phase and accumulated-phase images [17,18]. These dual-phase images may offer improved diagnostic performance for non-hypervascular hepatic lesions. The purpose of the current study was to examine the clinical significance of using contrast-enhanced ultrasound with Sonazoid to characterise focal hepatic lesions that show a non-hypervascular appearance on contrast-enhanced CT in patients with CLD.     

Correlation between computerised findings and Newman's scaling on vascularity using power Doppler ultrasonography imaging and its predictive value in patients with plantar fasciitis

Objectives

The purpose of this study was to correlate findings on small vessel vascularity between computerised findings and Newman''s scaling using power Doppler ultrasonography (PDU) imaging and its predictive value in patients with plantar fasciitis.

Methods

PDU was performed on 44 patients (age range 30–66 years; mean age 48 years) with plantar fasciitis and 46 healthy subjects (age range 18–61 years; mean age 36 years). The vascularity was quantified using ultrasound images by a customised software program and graded by Newman''s grading scale. Vascular index (VI) was calculated from the software program as the ratio of the number of colour pixels to the total number of pixels within a standardised selected area of proximal plantar fascia. The 46 healthy subjects were examined on 2 occasions 7–10 days apart, and 18 of them were assessed by 2 examiners. Statistical analyses were performed using intraclass correlation coefficient and linear regression analysis.

Results

Good correlation was found between the averaged VI ratios and Newman''s qualitative scale (ρ = 0.70; p<0.001). Intratester and intertester reliability were 0.89 and 0.61, respectively. Furthermore, higher VI was correlated with less reduction in pain after physiotherapeutic intervention.

Conclusions

The computerised VI not only has a high level of concordance with the Newman grading scale but is also reliable in reflecting the vascularity of proximal plantar fascia, and can predict pain reduction after intervention. This index can be used to characterise the changes in vascularity of patients with plantar fasciitis, and it may also be helpful for evaluating treatment and monitoring the progress after intervention in future studies.Plantar fasciitis is the most common cause of heel pain, and about 2 000 000 patients in the USA receive treatment every year because of this condition [1]. Besides mechanical loading, vascular disturbance with consequent metabolic impairment and hypoxia is thought to play an important role [2]. Indeed, fibrovascular hyperplasia and vascular proliferation were observed from microscopic specimens obtained from operative resection [3-5]. Walther et al [6] were the first group to evaluate plantar fascia vascularity non-invasively using power Doppler ultrasonography (PDU).PDU is one of the colour flow imaging techniques that encodes the amplitude of the power spectral density of the Doppler signals [7]. This method has been used to assess soft-tissue vascularity and treatment efficacy with a variety of musculoskeletal and related problems. Changes in vascularity in synovial tissues in patients with rheumatoid arthritis [8-11], osteoarthritis [12,13], tendinopathy [6,14-21] and plantar fasciitis [6] have been reported. Modulation in vascularity was observed in patients with tendinopathy after a course of intervention [14-21]. Most of these studies used the Newman''s grading scale to grade the tissue vascularity [19-21]. This qualitative grading for the PDU images had high correlation with the histopathological grading of vascularity of the synovial membrane in patients with arthritis [11]. Nevertheless, Newman''s grading system may not be objective and sensitive enough to differentiate subtle vascularity changes.Recently, computerised methods were used to quantify tissue vascularity with ultrasonography. Tissue vascularity was quantified by computing a vascular index (VI), which is calculated as the ratio of the number of colour pixels to the total number of pixels within the region of interest in patients with soft-tissue problems [8,9,11,17]. Note that most of these studies were conducted using colour Doppler ultrasonography. In this connection, PDU is superior to frequency-based colour Doppler ultrasonography, especially in tissues with low blood flow, such as the plantar fascia [6,22,23]. Ying et al [24] reported the feasibility of computerised quantification of vascularity in thyroid tissues with PDU. We were interested in evaluating whether the computerised quantification of vascularity could be applied on musculoskeletal tissue, such as the plantar fascia. Therefore, the purpose of the present study was to correlate the computerised VI and Newman''s qualitative grading scale in quantifying plantar fascia vascularity using PDU, to evaluate the intra- and intertester reliability of the computerised quantitative method and its predictive ability of recovery in patients with plantar fasciitis. Proximal plantar fascia, which is the most commonly affected area in individuals with plantar fasciitis, according to clinical examination [25,26] and previous B-mode ultrasonography [26-28], was chosen as the target testing area.     

Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with pathological examination

Objective

To investigate the correlation between enhancement patterns of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and pathological findings.

Methods

The CEUS enhancement patterns of 40 pathologically proven ICC lesions were retrospectively analysed. Pathologically, the degree of tumour cell and fibrosis distribution in the lesion was semi-quantitatively evaluated.

Results

4 enhancement patterns were observed in the arterial phase for 32 mass-forming ICCs: peripheral rim-like hyperenhancement (n=19); heterogeneous hyperenhancement (n=6); homogeneous hyperenhancement (n=3); and heterogeneous hypo-enhancement (n=4). Among the four enhancement patterns, the differences in tumour cell distribution were statistically significant (p<0.05). The hyperenhancing area on CEUS corresponded to more tumour cells for mass-forming ICCs. Heterogeneous hyperenhancement (n=2) and heterogeneous hypo-enhancement (n=2) were observed in the arterial phase for four periductal infiltrating ICCs. In this subtype, fibrosis was more commonly found in the lesions. Heterogeneous hyperenhancement (n=1) and homogeneous hyperenhancement (n=3) were observed in the arterial phase for four intraductal growing ICCs. This subtype tended to have abundant tumour cells.

Conclusion

The CEUS findings of ICC relate to the degree of carcinoma cell proliferation at pathological examination. Hyperenhancing areas in the tumour always indicated increased density of cancer cells.Intrahepatic cholangiocarcinoma (ICC) originates in the small bile duct and is grouped according to the International Classification of Diseases code, with hepatocellular carcinoma (HCC) being the primary liver tumour. It is the second most common primary liver tumour and is highly malignant. Although ICC is a relatively rare tumour, interest in this disease is rising because incidence and mortality rates for ICC are increasing steadily worldwide [1-5].ICC is notoriously difficult to diagnose and is usually fatal, owing to its late clinical presentation and the lack of effective non-surgical therapeutic modalities. It tends to present with non-specific symptoms such as malaise, weight loss and abdominal pain. Most patients have unresectable disease at presentation and die within 12 months from the effects of cancer cachexia and a subsequent rapid decline in performance status.According to growth characteristics, ICC is subcategorised into mass-forming, periductal infiltrating or intraductal-growing types by the Liver Cancer Study Group of Japan [6]. These subtypes show different biological behaviours and have different clinical outcomes. Mass-forming ICC spreads between hepatocyte plates and expands via the hepatic sinusoidal spaces. It often invades the adjacent peripheral branches of the portal vein. Periductal-infiltrating ICC tends to spread along the bile duct wall via the nerve and perineural tissue of Glisson''s capsule towards the porta hepatis. Intraductal-growing ICCs are usually small or polypoid and do not invade deeply into the submucosal layer, often spreading superficially along the mucosa surface. Characterisation of the tumours in terms of their growth pattern is necessary for optimal treatment planning and prognosis assessing. The prognosis for mass-forming and periductal-infiltrating cholangiocarcinoma is generally unfavourable, but is much better for the intraductal-growing type after surgical resection, and long-term patient survival can be expected [7,8].Contrast-enhanced ultrasound (CEUS) has been increasingly applied in liver imaging. By administration of ultrasound contrast agents, CEUS can display dynamic blood flow perfusion and microcirculation of liver lesions [9], similar to CT and MRI. In previous studies, CEUS had a similar diagnostic accuracy for ICC to CT and was suggested as an alternative diagnostic option when CT examination was not available for patients with iodine allergy or impaired renal function [10]. It was confirmed that CT and/or MRI findings of ICC were correlated with pathological findings; that is, the hyperenhancing areas always indicated a large number of tumour cells and the areas of delayed enhancement corresponded to fibrotic stroma at pathological examination. In addition, different morphological subtypes tended to exhibit distinct enhancement characteristics on CT [7,8,11-13]. On CEUS, besides the specific feature of peripheral rim-like hyperenhancement, diverse imaging findings of ICC were reported [9,10,14-17]. These different CEUS appearances may reflect the differences in pathological subtypes or components of ICC. The aim of this study was to investigate the correlation between the enhancement pattern of ICC on CEUS and pathological findings. This information may be useful for diagnosis, treatment planning and prognostic evaluation of ICC.     

Pulmonary tuberculosis associated with the reversed halo sign on high-resolution CT

We describe the case of a 32-year-old woman with pulmonary tuberculosis in whom a high-resolution CT scan demonstrated the reversed halo sign. The diagnosis of tuberculosis was made by lung biopsy and the detection of acid-fast bacilli in the sputum smear and culture. Follow-up assessment revealed a significant improvement in the lesions.The reversed halo sign is observed on high-resolution CT (HRCT) as a focal round area of ground-glass attenuation surrounded by a crescent or ring of consolidation [1, 2]. It was first described as being relatively specific for cryptogenic organising pneumonia [1], but was later observed in several other infectious [3–5] and non-infectious [6, 7] diseases.We report a case of a 32-year-old patient with tuberculosis who exhibited the reversed halo sign on chest CT. To our knowledge, this sign has not been previously described in an adult with pulmonary tuberculosis.     

Miliary tuberculosis: a comparison of CT findings in HIV-seropositive and HIV-seronegative patients

The aim of this study was to determine the differences in CT findings of miliary tuberculosis in patients with and without HIV infection. Two radiologists reviewed retrospectively the CT findings of 15 HIV-seropositive and 14 HIV-seronegative patients with miliary tuberculosis. The decisions on the findings were reached by consensus. Statistical analysis was performed using the χ² test, Mann–Whitney U-test and Fisher''s exact test. All of the HIV-seropositive and -seronegative patients had small nodules and micronodules distributed randomly throughout both lungs. HIV-seropositive patients had a higher prevalence of interlobular septal thickening (p = 0.017), necrotic lymph nodes (p = 0.005) and extrathoracic involvement (p = 0.040). The seropositive patients had a lower prevalence of large nodules (p = 0.031). In conclusion, recognition of the differences in the radiological findings between HIV-seropositive and -seronegative patients may help in the establishment of an earlier diagnosis of immune status in patients with miliary tuberculosis.Miliary tuberculosis (TB), which results from lympho-haematogenous dissemination of Mycobacterium tuberculosis, is a complication of both primary and post-primary TB [1, 2]. This disease results in the formation of small discrete foci of granulomatous tissue, which are uniformly distributed throughout the lung [3].An increase in TB incidence, including miliary TB, has been associated with infection by human immunodeficiency virus (HIV) [4]. In 2005, the World Health Organization estimated that 12% of HIV deaths globally were caused by TB, and that there were 630 000 new co-infections with TB and HIV [5]. Disseminated TB accounted for 5.4–8.1% of culture-confirmed TB cases, with 10–14% of patients coinfected with HIV having clinically recognisable dissemination [6, 7].Chest radiography may be helpful in the detection and final diagnosis of miliary TB. The characteristic radiographical findings consist of the presence of fine granular or numerous small nodular opacities measuring 1–3 mm in diameter scattered throughout both lungs [1, 3, 8, 9]. However, the radiograph may appear to be normal in the early stage of disease or in cases with nodules below the threshold of perceptibility; therefore, a diagnosis of miliary TB from chest radiographs can be difficult [10].Several studies have shown that CT imaging is more sensitive for the detection of parenchymal abnormalities in patients with AIDS who have active intrathoracic disease, and it has been suggested that CT may also be helpful in the differential diagnosis [11–14]. In addition, it has been reported that certain imaging techniques provided by multidetector-row CT are useful for the diagnosis of multiple micronodular infiltrative lung disease [15]. CT findings of miliary TB have been described in previous reports [16–18]; however, only a few studies on miliary TB in patients with HIV, particularly with reference to the CD4 count, have been reported [19, 20]. The radiographic manifestations of HIV-associated pulmonary TB are thought to be dependent upon the level of immunosuppression at the time of overt disease [21–23].The purpose of this study was to determine the differences in the CT findings of miliary TB for patients with and without HIV infection and to analyse any correlation between the CT features and the level of immunosuppression in patients.     

Assessment of ablative margin by MRI with ferucarbotran in radiofrequency ablation for liver cancer: comparison with enhanced CT

Objectives

Our aim was to determine whether ablated liver parenchyma surrounding a tumour can be assessed by MRI with ferucarbotran administered prior to radiofrequency ablation (RFA) compared with enhanced CT.

Methods

55 hepatocellular carcinomas (HCCs) in 42 patients and 5 metastatic liver cancers in 3 patients were treated by RFA after ferucarbotran administration. We then performed T₂* weighted MRI after 1 week and enhanced CT after 1 month. T₂* weighted MRI demonstrated the ablated parenchyma as a low-intensity rim around the high intensity of the ablated tumour in these cases. The assessment was allocated to one of three grades: margin (+), high-intensity area with continuous low-intensity rim; margin zero, high-intensity area with discontinuous low-intensity rim; and margin (−), high-intensity area extending beyond the low-intensity rim.

Results

Margin (+), margin zero and margin (−) were found in 17, 35 and 5 nodules, respectively. All 17 nodules with margin (+) and 13 of those with margin zero were assessed as having sufficient abalative margins on CT. The remaining 22 nodules with margin zero had insufficient margins on CT. The overall agreement between MRI and CT for the diagnosis of the ablative margin was moderate (κ=0.507, p<0.001). No local recurrence was found in 15 HCC nodules with margin (+), whereas local recurrence was found in 4 (11.8%) out of 34 HCC nodules with margin zero.

Conclusion

Administration of ferucarbotran before RFA enables the ablative margin to be visualised as a low-intensity rim, and also enables the evaluation of the ablative margin to be made earlier and more easily than with enhanced CT.Radiofrequency ablation (RFA) has become a widely used treatment for hepatocellular carcinoma (HCC) [1], with some studies reporting significant long-term survival results [2,3]. One of the most difficult and troublesome issues in RFA is the lack of a reliable method for confirming that complete necrosis has been achieved in the treated lesion. CT and MRI are commonly used to evaluate the therapeutic response in the ablated tumours. The imaging hallmark of successful treatment is a lack of enhancement in the index tumour on CT or MRI [4,5]. However, previous pathological examination has demonstrated the presence of microsatellite nodules around the original tumour [6,7]. Therefore, it is necessary to ablate liver parenchyma surrounding the original tumour, as well as the tumour itself, and the ablation zone of the surrounding normal tissue needs to be recognised. In fact, several studies [8-10] have reported that the local recurrence rate in nodules with sufficient ablative margin is lower than that in those without sufficient ablative margin. The ablative margin is conventionally assessed by comparing enhanced CT images before and after RFA for HCC tumours.Mori et al [11] reported a new method of evaluating the ablative margin using ferucarbotran (Resovist; Bayer Schering Pharma, Berlin, Germany), and demonstrated that the ablative margin is easily assessed by MRI. Ferucarbotran is a clinically approved superparamagnetic iron oxide (SPIO) that is liver specific on MRI. It is composed of SPIO microparticles (γ-Fe₂O₃) coated with carboxydextran. After intravenous administration, ferucarbotran is phagocytosed by Kupffer cells and equally distributed throughout the entire liver [12]. Kupffer cells are much more dominant in hepatic parenchyma than in cancer tissue. Therefore, the signal intensity from cancer in T₂* weighted sequences becomes relatively high compared with that from hepatic parenchyma. Ferucarbotran in ablated hepatic parenchyma would remain after ablation, showing low intensity around high-intensity cancer on post-ablational MR images.The aim of this study was to determine the usefulness of ablative margin assessment by enhanced MRI using ferucarbotran administered before RFA in patients with liver cancer in comparison with post-ablation enhanced CT images after 1 month.     

Hepatocellular carcinoma in cirrhotic patients at multidetector CT: hepatic venous phase versus delayed phase for the detection of tumour washout

Objectives

Our aim was to compare retrospectively hepatic venous and delayed phase images for the detection of tumour washout during multiphasic multidetector row CT (MDCT) of the liver in patients with hepatocellular carcinoma (HCC).

Methods

30 cirrhotic patients underwent multiphasic MDCT in the 90 days before liver transplantation. MDCT was performed before contrast medium administration and during hepatic arterial hepatic venous and delayed phases, images were obtained at 12, 55 and 120 s after trigger threshold. Two radiologists qualitatively evaluated images for lesion attenuation. Tumour washout was evaluated subjectively and objectively. Tumour-to-liver contrast (TLC) was measured for all pathologically proven HCCs.

Results

48 HCCs were detected at MDCT. 46 of the 48 tumours (96%) appeared as either hyper- or isoattenuating during the hepatic arterial phase subjective washout was present in 15 HCCs (33%) during the hepatic venous phase and in 35 (76%) during the delayed phase (p<0.001, McNemar’s test). Objective washout was present in 30 of the 46 HCCs (65%) during the hepatic venous phase and in 42 of the HCCs (91%) during the delayed phase (p=0.001). The delayed phase yielded significantly higher mean TLC absolute values compared with the hepatic venous phase (−16.1±10.8 HU vs −10.5±10.2 HU; p<0.001).

Conclusions

The delayed phase is superior to the hepatic venous phase for detection of tumour washout of pathologically proven HCC in cirrhotic patients.Multiphasic contrast-enhanced multidetector row CT (MDCT) plays a pivotal role in the diagnostic work-up of cirrhotic patients, who are at increased risk of developing hepatocellular carcinoma (HCC) [1]. Increased enhancement of the tumour compared with the surrounding liver parenchyma during the hepatic arterial phase is the cornerstone for the diagnosis of HCC at multiphasic MDCT [1,2]. However, a variety of entities—dysplastic nodules [3], confluent hepatic fibrosis [4], non-tumourous arterioportal shunts [5] and haemangioma [6]—can also manifest with increased arterial enhancement and thus mimic HCC, particularly if they are smaller than 2 cm in diameter.Tumour washout, i.e. hypoattenuation relative to the adjacent hepatic parenchyma during the hepatic venous or delayed phase, has been recognised as a strong predictor of HCC [7,8]. This sign has been included, along with the presence of hypervascularity, in the latest American Association for the Study of Liver Diseases (AASLD) guidelines for the diagnosis of HCC at multiphasic MDCT, MRI or contrast-enhanced ultrasonography [1]. Although it is well known that tumour enhancement is best visualised during the late hepatic arterial phase [9,10], there is no consensus regarding the correct timing for the detection of tumour washout at multiphasic MDCT of the liver. Most commonly, the hepatic arterial phase is followed by the hepatic venous phase, acquired 60–70 s after injection of contrast material [9-12]. In addition, a delayed phase, acquired from 2–10 min after contrast material injection, can follow the hepatic venous phase [13-20] or can occur alone after the hepatic arterial phase [21-23]. Regardless of the phase sequence chosen, to the best of our knowledge, no study has yet compared the hepatic venous and delayed phases for the detection of tumour washout in patients with HCC. The purpose of our study was to compare retrospectively the hepatic venous and delayed phases for the detection of tumour washout during multiphasic MDCT of the liver in patients with HCC who underwent liver transplantation.     

Inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64-row CT: an anthropomorphic phantom study

Objective:

To assess inter- and intrascanner variability in volumetry of solid pulmonary nodules in an anthropomorphic thoracic phantom using low-dose CT.

Methods:

Five spherical solid artificial nodules [diameters 3, 5, 8, 10 and 12 mm; CT density +100 Hounsfield units (HU)] were randomly placed inside an anthropomorphic thoracic phantom in different combinations. The phantom was examined on two 64-row multidetector CT (64-MDCT) systems (CT-A and CT-B) from different vendors with a low-dose protocol. Each CT examination was performed three times. The CT examinations were evaluated twice by independent blinded observers. Nodule volume was semi-automatically measured by dedicated software. Interscanner variability was evaluated by Bland–Altman analysis and expressed as 95% confidence interval (CI) of relative differences. Intrascanner variability was expressed as 95% CI of relative variation from the mean.

Results:

No significant difference in CT-derived volume was found between CT-A and CT-B, except for the 3-mm nodules (p<0.05). The 95% CI of interscanner variability was within ±41.6%, ±18.2% and ±4.9% for 3, 5 and ≥8 mm nodules, respectively. The 95% CI of intrascanner variability was within ±28.6%, ±13.4% and ±2.6% for 3, 5 and ≥8 mm nodules, respectively.

Conclusion:

Different 64-MDCT scanners in low-dose settings yield good agreement in volumetry of artificial pulmonary nodules between 5 mm and 12 mm in diameter. Inter- and intrascanner variability decreases at a larger nodule size to a maximum of 4.9% for ≥8 mm nodules.

Advances in knowledge:

The commonly accepted cut-off of 25% to determine nodule growth has the potential to be reduced for ≥8 mm nodules. This offers the possibility of reducing the interval for repeated CT scans in lung cancer screenings.Lung cancer is the primary cancer in males and the second most common cancer in females worldwide, causing 18% of the total number of deaths [1]. Many lung cancers are found at a relatively late stage, resulting in a 5-year survival of only 15% or less [2]. Low-dose CT is a promising screening method for early detection of lung cancer [3–7]. The first result indicates that CT lung cancer screening can reduce lung cancer-specific mortality [8].In lung cancer screening, treatment decisions usually depend on pulmonary nodule size for the nodules at first detection and on the growth rate at follow-up [4]. Therefore, it is essential to assess the nodule size and growth rate accurately and reproducibly [9,10]. Variability has been found in CT-derived nodule size assessment [11,12]. In view of the current practice of patients frequently undergoing follow-up examinations, sometimes not on the same scanner, reliable inter- and intrascanner reproducibility of nodule volumetry is important.However, previous studies reported inconsistent results regarding the reproducibility of nodule volumetry. Some in vitro studies have been performed in which artificial nodules were placed at known locations in a thoracic phantom without pulmonary vessels [13–15]. Some of these studies were based on older generation CT scanners [13,16]. These studies generally showed a small margin of variability in nodule volumetry for software from different vendors. On the other hand, in vivo studies have shown that variability can be considerable, with variability up to 25% for 15 to 500 mm³ nodules [11,17–19]. A study to investigate inter- and intrascanner variability under optimally controlled conditions, yet resembling human lungs, using a more realistic phantom, has not been performed. Nowadays, 64-row multidetector CT (64-MDCT) scanners are most commonly utilised, as well as in lung cancer screenings. The variability of nodule volumetry of these scanners impacts nodule management, e.g. the interval of repeated CT scanning. As an extension to our recent study on observer detection and accuracy of manual and semi-automated volumetry [10], the focus of this study is on reproducibility between and within 64-MDCT systems. We assessed the inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64-MDCT, using randomly placed solid nodules in an anthropomorphic thoracic phantom with a background of pulmonary vasculature.     

Non-osseous incidental findings in low-dose whole-body CT in patients with multiple myeloma

Objective:

The purpose of this study was to identify the frequency and grading of non-osseous incidental findings (NOIF) in non-contrast whole-body low-dose CT (LDCT) in patients with multiple myeloma.

Methods:

In the time period from 2010 to 2013, 93 patients with multiple myeloma were staged by non-contrast whole-body LDCT at our radiological department. LDCT images were analysed retrospectively for NOIF, which also included unsuspected extramedullary manifestation of multiple myeloma. All NOIF were classified as major or clinically significant, moderate or possibly clinically significant and minor or not clinically significant. Medical records were analysed regarding further investigation and follow-up of the identified NOIF.

Results:

In the 93 patients, 295 NOIF were identified (on average, 3.2 NOIF per patient). Most of the NOIF (52.4%) were not clinically significant, 25.8% of the NOIF were possibly clinically significant and 21.8% of the NOIF were clinically significant. Clinically significant NOIF were investigated further by CT after intravenous administration of contrast medium and/or by ultrasound or MRI. In 34 of these cases, extramedullary relapse of myeloma, occult carcinoma or infectious/septic incidental findings were diagnosed (11.5% of all NOIF). In the remaining 10.3% of the NOIF classified as clinically significant, various benign lesions were diagnosed.

Conclusion:

LDCT detected various non-osseous lesions in patients with multiple myeloma. 36.6% of the patients had clinically significant NOIF. Therefore, LDCT examinations in patients with multiple myeloma should be evaluated carefully for the presence of NOIF.

Advances in knowledge:

LDCT identified several NOIF. A total of 36.6% of patients with multiple myeloma had clinically significant NOIF. Radiologists should analyse LDCT examinations in patients with multiple myeloma not only for bone lesions, but also for lesions in other organs.CT is used for screening or staging in several malignancies.^1–8 As reported previously, the staging CT examination also provides additional information regarding the general health status of the patient or so-called incidental findings (IF).^1,3,6,7 Several IF on CT examinations were described in the literature.^1–6 According to previous reports, IF can be classified into five different categories: Group “0”, limited examination, that is, evaluation of IF are severely limited; Group “1”, normal findings or anatomic variant; Group “2”, clinically unimportant findings, such as liver or kidney cysts; Group “3”, likely unimportant findings; and Group “4”, potentially important findings, such as solid renal masses or lymphadenopathy.⁵ In another publication, a three-part classification of IF according to their clinical importance was proposed, namely major, moderate and minor IF.¹Most of the IF are clinically non-significant, such as colonic diverticula or simple cysts.^1–7 However, serious IF, such as aortic aneurysm or dissection, thrombosis, pulmonary embolism and second primary tumours, can also occur,^1,3,6,7 and some of them may be not visible on low-dose CT (LDCT).Most reports regarding IF are based on contrast-enhanced CT.^1,7,9–11 There are only a few reports regarding IF in LDCT.¹² They described IF in screening programmes for lung cancer and based the findings on thoracic LDCT only.¹² In addition, non-contrast LDCT has been established for staging of bone lesions in multiple myeloma.^13–16 However, radiologists should analyse LDCT examinations not only for bone lesions but also for lesions in other organs, which may include extramedullary manifestation of multiple myeloma as well as unrelated IF.Although IF in multiple myeloma have also been described previously,¹⁴ to the best of our knowledge, there exists no analysis focused on frequency and distribution of non-osseous IF (NOIF) on whole-body LDCT. Therefore, the purpose of this study was to identify the frequency and grading of NOIF in non-contrast whole-body LDCT in patients with multiple myeloma.     

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma

Objective

To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC).

Methods

From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion.

Results

The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI–CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05).

Conclusions

Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease.

Advances in knowledge

There were discrepancies of approximately 5 mm in gated MRI–CT fusion planning for HCC patients.Many studies have reported that the treatment response and survival of hepatocellular carcinoma (HCC) patients are related to the delivered radiation dose [1-3]. Recently, detailed information on HCC and liver motion gained from the use of advanced techniques, such as a fiducial marker combined with four-dimensional (4D) planning CT, has enabled the delivery of higher doses of radiation therapy (RT) with reduced normal liver toxicity [3-5].Although triphasic CT can provide much information about HCC, the lesion/liver contrast is higher in MRI than in CT [6,7]. To take advantage of these benefits, there have been many efforts to incorporate liver MRI in the RT planning process [8,9]. Moreover, several groups have demonstrated the feasibility of using cine-MRI and 4D-MRI to measure liver tumour motion for RT planning [10-12]. However, a consensus has not yet been reached on the best strategies to compensate for liver motion and adapt RT planning and delivery using planning 4D-CT combined with liver MRI.The primary goal of this prospective study was to evaluate the accuracy of gated MRI and 4D-CT fusion planning by measuring the discrepancies in the specific anatomical landmark points of the liver between exhale-phase images of gated liver MRI and 4D-CT. We also evaluated possible factors affecting gated liver MRI and 4D-CT fusion discrepancy and RT response.     

Simplified rules for everyday delineation of lymph node areas for breast cancer radiotherapy

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas “Help of delineation for breast cancer treatment”. In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.The value of lymph node irradiation has already been demonstrated by various studies and meta-analyses [1–3]. In the age of new conformal techniques, there is a real need for a clear definition of treated volumes, such as breast, tumour bed, lymph node areas and organs at risk (OAR) [4–10]. Many teams have been working for several years on the definition of treated volumes. Some delineation studies are exclusively theoretical and some provide a good anatomical atlas, but this information is difficult to use in everyday practice [4–15]. The treatment position has also been shown to be an important factor of variability in the depth and situation of lymph node volumes [5, 6]. Conformal and intensity-modulated radiotherapy (IMRT) require an exact definition of target volumes in terms of their anatomical limits for delineation on CT scans. Some authors have proposed anatomically based landmarks specific for breast cancer radiotherapy in order to delineate all regional lymph nodes and the breast [5, 6, 8, 10, 15, 16]. Despite this work, two recent papers have demonstrated the individual interobserver variability and differences in target and OAR delineation for breast irradiation, especially in lymph node areas [7, 8].This study was designed to propose a practical method to improve and facilitate the everyday delineation process for the clinicians of our department.     

Accessory or additional renal arteries show no relevant effects on the width of the upper urinary tract: a 64-slice multidetector CT study in 1072 patients with 2132 kidneys

Objective

The aim of this study was to find out on an unselected patient group whether crossing vessels have an influence on the width of the renal pelvis and what independent predictors of these target variables exist.

Methods

In this cross-sectional study, 1072 patients with arterially contrasted CT scans were included. The 2132 kidneys were supplied by 2736 arteries.

Results

On the right side, there were 293 additional and accessory arteries in 286 patients, and on the left side there were 304 in 271 patients. 154 renal pelves were more than 15 mm wide. The greatest independent factor for hydronephrosis on one side was hydronephrosis on the contralateral side (p<0.0001 each). Independent predictors for the width of the renal pelvis on the right side were the width of the renal pelvis on the left, female gender, increasing age and height; for the left side, predictors were the width of the renal pelvis on the right, concrements, parapelvic cysts and great rotation of the upper pole of the kidney to dorsal. Crossing vessels had no influence on the development of hydronephrosis. Only anterior crossing vessels on the right side are associated with widening of the renal pelvis by 1 mm, without making it possible to identify the vessel as an independent factor in multivariate regression models.

Conclusion

The width of the renal pelvis on the contralateral side is the strongest independent predictor for hydronephrosis and the width of the renal pelvis. There is no link between crossing vessels and the width of the renal pelvis.Obstructions of the ureteropelvic junction (UPJ) can be caused by intrinsic or extrinsic factors [1]. Although there are no studies of this to date, crossing the UPJ by an aberrant crossing vessel is considered the most important [2] of the extrinsic factors [3]. Crossing vessels, which are thought to cause from 40% to over 50% of the extrinsic UPJ obstructions in adults [4, 5], are located ventral more often than dorsal to the UPJ. These are usually normal vessels of the lower pole segment [4, 6–9], which can be divided into additional renal arteries arising from the aorta, and accessoric renal arteries arising from branches of the aorta [10, 11]. The primary surgical therapy of choice is endoscopic endopyelotomy [12]. The success rate of 89–90% [12, 13] is thought to be noticeably poorer in patients with crossing vessels [12, 13]; however, this is not undisputed [14, 15]. Be that as it may, to prevent bleeding complications it is necessary to be familiar with the vascular situation around the UPJ prior to the procedure [3, 16–18]. CT angiography is used for this purpose, as it is highly accurate, quick to perform and shows all relevant anatomical structures in relation to one another [3, 19, 20]. The objective of this study was to determine whether or not there are vascular morphological patterns or other factors that influence the width of the renal collecting system, regardless of the definitions of hydronephrosis.     

Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis

Objective

This study aimed to compare thin-section CT images from sarcoidosis patients who had either normal or elevated serum KL-6 levels.

Methods

101 patients with sarcoidosis who underwent thin-section CT examinations of the chest and serum KL-6 measurements between December 2003 and November 2008 were retrospectively identified. The study group comprised 75 sarcoidosis patients (23 male, 52 female; aged 19–82 years, mean 54.1 years) with normal KL-6 levels (152–499 U ml^–1, mean 305.7 U ml^–1) and 26 sarcoidosis patients (7 male, 19 female; aged 19–75 years, mean 54.3 years) with elevated KL-6 levels (541–2940 U ml^–1, mean 802.4 U ml^–1). Two chest radiologists, unaware of KL-6 levels, retrospectively and independently interpreted CT images for parenchymal abnormalities, enlarged lymph nodes and pleural effusion.

Results

CT findings in sarcoidosis patients consisted mainly of lymph node enlargement (70/75 with normal KL-6 levels and 21/26 with elevated KL-6 levels), followed by nodules (50 and 25 with normal and elevated levels, respectively) and bronchial wall thickening (25 and 21 with normal and elevated levels, respectively). Ground-glass opacity, nodules, interlobular septal thickening, traction bronchiectasis, architectural distortion and bronchial wall thickening were significantly more frequent in patients with elevated KL-6 levels than those with normal levels (p<0.001, p<0.005, p<0.001, p<0.001, p<0.001 and p<0.001, respectively). By comparison, there was no significant difference in frequency of lymph node enlargement between the two groups.

Conclusion

These results suggest that serum KL-6 levels may be a useful marker for indicating the severity of parenchymal sarcoidosis.KL-6 is a mucin-like high molecular weight glycoprotein that is expressed on Type II pneumocytes and respiratory bronchiolar epithelial cells in the normal lung [1, 2]. Serum levels of KL-6 are elevated in various respiratory and non-respiratory conditions, including breast and pancreatic cancers [3, 4] and diabetes mellitus [5]. This observation has led to a focus on the use of KL-6 as a diagnostic and prognostic tool in respiratory diseases.Serum and bronchoalveolar lavage fluid levels of KL-6, first described by Kohno et al [6] in 1988, were raised in patients with interstitial pneumonia [1, 2, 7]. Several investigators have also reported that KL-6 is a useful serum marker to confirm diagnosis and for long-term management in patients with diffuse pulmonary diseases, particularly interstitial lung diseases. Patients with idiopathic pulmonary fibrosis or non-specific interstitial pneumonia showed significantly elevated KL-6 levels [8-13].Several studies indicate that the serum KL-6 level is elevated in patients with sarcoidosis [14-16]. However, no studies describing radiological findings comparing thin-section CT images between patients with elevated KL-6 levels and those with normal KL-6 levels have been published in the English language literature.Thus, we aimed to retrospectively evaluate and compare pulmonary CT findings between patients with elevated KL-6 levels and those with normal KL-6 levels.     

Pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy

Objective:

To describe the pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer.

Methods:

A cohort of patients undergoing weekly CT scans during dose-painted IMRT was considered. The parotid glands were contoured at the time of treatment planning (baseline) and on all subsequent scans. For a given patient, the parotid glands were labelled as higher (H) and lower (L), based on the mean dose at planning. The volume of each gland was determined for each scan and the percent change from baseline computed. Data were fit to both linear and quadratic functions. The role of selected covariates was assessed with both logistic regression and pair-wise comparison between the sides. The analyses were performed considering the whole treatment duration or each separate half.

Results:

85 patients, 170 glands and 565 scans were analysed. For all parotids except one, the quadratic function provided a better fit than the linear one. Moreover, according to both the logistic regression and pair-wise comparison, the cumulative mean dose of radiation is independently correlated with the parotid shrinkage during the first but not the second half of the treatment. Conversely, age and weight loss are predictors of relative parotid shrinkage during the entire course of the treatment.

Conclusion:

Parotid gland shrinkage during IMRT is not linear. Age, weight loss and radiation dose independently predict parotid shrinkage during a course of IMRT.

Advances in knowledge:

The present study adds to the pathophysiology of parotid shrinkage during radiotherapy.Fractionated radiotherapy is based on the assumption that the dose distribution obtained at planning is delivered during each treatment session. However, both set-up errors and tissue deformation can modify the dose that is administered. Shifts in the location of isodose levels compared with planning become critical for techniques that are highly conformal to the target(s), such as IMRT, justifying the interest in image guidance and adaptive radiotherapy [1]. Because of the sharp dose gradient around the target(s), subtle changes in the relative position or in the volume of organs at risk may alter the planned dose that the volume of an organ receives, as has been shown for the parotid glands [2–6].In a study by Ricchetti et al [7], we found that the parotid glands are the regions of interest that undergo the largest absolute and relative changes in volume during treatments. Although at least 16 articles have documented a significant percent reduction in the volume of the parotid gland during the course of fractionated radiotherapy [2,3,7–20], there are still several unanswered questions. It is unclear why some parotid glands shrink to about 50–60% during treatment, while others show only minimal changes. Studies that have investigated predictors of shrinkage have suggested weight loss during treatment, patient age and dose of radiation to the parotid as potential factors [2,9,16–19]. However, results are inconsistent [3,8,10,14]. Some studies have suggested that dosimetrically spared parotid glands undergo only minimal volume changes during treatment [16,18], whereas others describe a similar behaviour regardless of the radiation dose [7,8,10]. Furthermore, it is unclear whether the daily percent volume change is constant [8,10,16,19] or variable [7,10,13] during the course of treatment. A variable daily percent change in the volume may indicate that there are predictive factors specific to certain portions of the fractionated radiation schedule. In the present article, we attempt to clarify these points.     

Misplaced pulmonary arteries in an adult patient with pulmonary hypertension

Misalignment of pulmonary vessels, with or without alveolar capillary dysplasia, is a rare cause of persistent pulmonary hypertension in the newborn. The prognosis is poor, with virtually all patients succumbing to unremitting hypoxaemic respiratory failure and death during the newborn period. We report the CT and histological findings of misplaced pulmonary arteries in a previously healthy young adult patient who presented with pulmonary arterial hypertension. Contiguous high-resolution spiral CT angiography showed small pulmonary arteries coursing within the interlobular septa and enlarged central pulmonary arteries. Surgical lung biopsy demonstrated anomalous muscularised pulmonary arteries in the interlobular septa. This is, to our knowledge, the first report of misplaced pulmonary arteries presenting in an adult patient and may represent a forme fruste of the neonatal vascular anomaly. A possible association with pulmonary arterial hypertension is also suggested in this case.Misalignment of pulmonary vessels, with or without alveolar capillary dysplasia (ACD), is a rare cause of persistent pulmonary hypertension in the newborn [1–5]. The prognosis is poor, with patients usually succumbing to unremitting hypoxaemic respiratory failure and death in early infancy [3–7]. We report the CT and histological findings of misplaced pulmonary arteries in a previously healthy young adult patient who presented with symptoms of pulmonary arterial hypertension. CT of the chest confirmed the findings of pulmonary arterial hypertension and demonstrated small anomalous pulmonary arteries within many interlobular septa. Surgical lung biopsy confirmed the presence of anomalous muscularised small pulmonary arteries in the interlobular septa. To our knowledge, this is the first reported adult patient with a histological diagnosis of misplaced pulmonary arteries in the literature and may represent a variant of misalignment of pulmonary vessels seen in neonates. This finding lends credence to earlier assertions that the distribution of the vascular misalignment, be it patchy or diffuse, may correlate with the phenotypic expression of disease [3, 6, 7]. The finding in an adult without associated ACD would seem to validate previous hypotheses that the anomalies may co-exist or present as mutually exclusive entities [2–5].     

Comparison of mammography, sonography, MRI and clinical examination in patients with locally advanced or inflammatory breast cancer who underwent neoadjuvant chemotherapy

Objectives

The purpose of this study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced or inflammatory breast cancer. Each prediction method was compared with the gold standard of surgical pathology.

Methods

43 patients (age range, 25–62 years; mean age, 42.7 years) with locally advanced or inflammatory breast cancer who had been treated by neoadjuvant chemotherapy were enrolled prospectively. We compared the predicted residual tumour size and the predicted response on imaging and clinical examination with residual tumour size and response on pathology. Statistical analysis was performed using weighted kappa statistics and intraclass correlation coefficients (ICC).

Results

The ICC values between predicted tumour size and pathologically determined tumour size were 0.65 for clinical examination, 0.69 for mammography, 0.78 for sonography and 0.97 for MRI. Agreement between the response predictions at mid-treatment and the responses measured by pathology had kappa values of 0.28 for clinical examination, 0.32 for mammography, 0.46 for sonography and 0.68 for MRI. Agreement between the final response predictions and the responses measured by pathology had kappa values of 0.43 for clinical examination, 0.44 for mammography, 0.50 for sonography and 0.82 for MRI.

Conclusion

Predictions of response and residual tumour size made on MRI were better correlated with the assessments of response and residual tumour size made upon pathology than were predictions made on the basis of clinical examination, mammography or sonography. Thus, the evaluation of predicted response using MRI could provide a relatively sensitive early assessment of chemotherapy efficacy.The advantages of neoadjuvant chemotherapy are multiple and it has been used widely during the past few years [1]. Its primary role is to induce tumour shrinkage and permit breast-conserving surgery, primarily in patients with advanced breast cancer [2-4]. Neoadjuvant chemotherapy allows earlier treatment of micrometastatic disease and the study of biological markers that might predict tumour response [5]. The effectiveness of chemotherapeutic agents in treating both primary breast cancer and potential metastatic disease may be enhanced by the presence of tumour neovascularity. If chemotherapy is given before surgery, while tumour vascularity remains intact, the chemotherapeutic agents may be better able to reach the tumour and thus be more effective.Neoadjuvant chemotherapy of locally advanced breast cancer (LABC) has also been shown to improve the resectability rate, offering disease-free and overall survival rates that are at least equivalent to those offered by surgery alone [6,7]. Pathological complete response (pCR) is clinically significant because it is associated with improved long-term prognosis and decreased risk of recurrence [6,8]. Decisions regarding the continuation of current regimens and the appropriate type and timing of surgery depend on the radiological and clinical assessment of residual tumour size during neoadjuvant chemotherapy [9,10]. Until now, many studies have shown that physical examinations, mammography and sonography provide suboptimal evaluations of lesion extent that do not allow accurate assessments of pathological response or residual tumour size [5^,11-13]. In the case of LABC, physical examination, mammography or sonography may be suitable for detecting the larger lesions of non-responders, but they have limited sensitivity for responders with smaller residual lesions [14,15]. For mammography, calcifications may persist or even increase in patients who respond to neoadjuvant chemotherapy [14,16,17].Many previous studies have shown that MRI is the most reliable technique for evaluating residual disease after neoadjuvant chemotherapy, although initial reports described frequent false-negatives with smaller-volume disease [18-27]. Recent studies have increased the sensitivity of MRI, with increased resolution, reduced slice thickness and lower enhancement thresholds being used to minimise the underestimation of residual disease [15^,22-27]. It is still difficult, however, to distinguish residual scarring, necrosis and fibrosis from viable residual malignancy and to predict accurate response after neoadjuvant chemotherapy, especially in responders. Few published studies have described work with patients with inflammatory breast cancer who underwent neoadjuvant chemotherapy because the incidence of this disease is very low [28,29]. The purpose of our study was to determine the relative accuracies of mammography, sonography, MRI and clinical examination in predicting residual tumour size and pathological response after neoadjuvant chemotherapy for locally advanced and inflammatory breast cancer. We compared each prediction method with the gold standard of surgical pathology.     

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

Objective

To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.

Methods

43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis.

Results

CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm.

Conclusion

CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies.Carcinoma of the urinary bladder is the most common malignancy of the urinary tract that must be ruled out in patients with haematuria with negative upper urinary tract findings [1]. Cystoscopy remains the most sensitive method of detecting bladder cancer, but has several limitations: it is an invasive procedure; it is uncomfortable in some patients and it requires sedation or anaesthesia. Conventional ultrasound (US) is one of the imaging techniques used to screen for bladder cancer, but with variable accuracy. The best results are obtained using the latest equipment and new imaging tools such as three-dimensional (3D) ultrasound [2-5]. Angiogenesis is essential to allow growth of malignancies, and the detection of tumoural neovascularisation is one of the keys of imaging modalities to achieve a definite diagnosis. CT and MRI are accurate techniques for bladder cancer detection when they are performed with the injection of intravascular contrast agents. Detection relies on the identification of bladder cancer neovascularisation and recent studies have shown high accuracy with both techniques [6,7]. The introduction of microbubble contrast agents and the development of contrast-specific software have increased the value of ultrasound in the field of oncology [8,9]. Ultrasound contrast agents are strictly intravascular and are very sensitive in revealing tumour microvascularisation, helping in the detection and characterisation of malignancies [10-13]. Recently, the behaviour of bladder cancer has been described after the administration of ultrasound contrast agent, and its diagnosis relies on the detection of hypervascular wall bladder thickening [14].The aim of our study was to retrospectively assess the value of contrast-enhanced ultrasound (CEUS) in bladder cancer detection in a selected high-risk group of patients using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound.